Depressive Episodes, Depressive Syndrome, Major Depressive Disorder (MDD)
Conditions
Keywords
MaintenanceTMS, NIBS, TaperingTMS, ClusterTMS, MDD, DepressiveSyndrome
Brief summary
The goal of this clinical trial is to compare two maintenance transcranial magnetic stimulation (rTMS) strategies following successful acute theta burst stimulation (TBS) treatment in adults with depressive syndrome. It will also evaluate whether the two maintenance strategies differ in their ability to maintain the antidepressant treatment response over 24 weeks. The main questions it aims to answer are: Does clustered maintenance rTMS reduce the risk of depressive relapse or clinically relevant symptom worsening compared with tapered maintenance rTMS? Do the two maintenance strategies differ in depressive symptoms, global clinical status, psychosocial functioning, and MRI-based biomarkers over time? Researchers will compare a clustered maintenance rTMS protocol with a tapered maintenance rTMS protocol. Participants will: * Complete successful acute TBS treatment before study enrollment * Be randomly assigned to either clustered or tapered maintenance rTMS * Receive 20 maintenance stimulation sessions over 20 weeks * Attend clinical follow-up assessments every 4 weeks for a total follow-up -period of 24 weeks * Undergo optional multimodal MRI examinations at the Munich study site
Detailed description
Repetitive transcranial magnetic stimulation (rTMS), including intermittent theta burst stimulation (iTBS), is an established treatment for depressive disorders. While the efficacy of acute treatment has been demonstrated in numerous clinical trials, a substantial proportion of patients experience symptom worsening or relapse following successful acute treatment if no maintenance therapy is provided. Several maintenance strategies have been proposed, including tapered treatment schedules with gradually decreasing treatment frequency and clustered treatment schedules consisting of repeated blocks of consecutive stimulation sessions. However, the available evidence is limited, and no randomized controlled trial has directly compared these two maintenance approaches using identical treatment duration and the same total number of stimulation sessions. This prospective, randomized, controlled, two-center study aims to compare two maintenance treatment strategies following successful acute iTBS in adults with depressive syndrome. Patients who achieve response or remission after a standardized acute iTBS treatment course will be randomized in a 1:1 ratio to either a tapered maintenance protocol or a clustered maintenance protocol. Randomization will be stratified by study site and baseline depression severity. Because of the different treatment protocols, blinding of participants and treating clinicians is not feasible. MRI data analyses will be performed blinded to treatment allocation. Both maintenance protocols include 20 stimulation sessions delivered over a 20-week maintenance period following a four-week stimulation-free interval after completion of the acute treatment phase. The treatment protocols differ only in the temporal distribution of maintenance sessions. The tapered protocol gradually reduces treatment frequency over time, whereas the clustered protocol delivers stimulation in four clusters of five consecutive daily sessions. The primary objective is to compare the time to depressive relapse or clinically relevant symptom worsening during the 24-week follow-up period. Clinically relevant symptom worsening is defined using predefined changes in the Montgomery-Åsberg Depression Rating Scale (MADRS), and relapse is defined as the recurrence of at least moderate depressive symptoms together with loss of the previously achieved treatment response. Secondary objectives include comparing longitudinal changes in depressive symptom severity, patient-reported depressive symptoms, global clinical status, and psychosocial functioning using the MADRS, Beck Depression Inventory (BDI), Clinical Global Impression (CGI), and Global Assessment of Functioning (GAF), respectively. An additional objective of the study is to investigate neurobiological correlates of maintenance treatment using multimodal magnetic resonance imaging (MRI). At the Munich study site, participants will be offered optional multimodal MRI examinations. Participation in the MRI component is voluntary and is not required for participation in the clinical trial. MRI assessments include resting-state functional MRI, arterial spin labeling, diffusion imaging including NODDI, and quantitative MRI. These analyses aim to identify imaging biomarkers associated with maintenance of antidepressant effects, symptom worsening, and relapse risk following maintenance iTBS. Participation in the MRI component is optional and is not required for participation in the clinical trial.
Interventions
DEVICERepetitive Transcranial Magnetic Stimulation (rTMS), Theta Burst Stimulation
Participants receive maintenance rTMS treatment (intermittent theta burst stimulation) following successful acute iTBS treatment. Participants are randomized to either a tapered or a clustered maintenance protocol. Both protocols consist of 20 maintenance stimulation sessions delivered over 20 weeks following a four-week stimulation-free interval but differ in the temporal distribution of stimulation sessions.
Sponsors
Technical University of Munich
Medizinische Universitätsklinik Tübingen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
MRI data analyses will be performed blinded to treatment allocation. Participants and treating clinicians are not blinded because of the different treatment protocols.
Intervention model description
Participants who achieve response or remission following standardized acute theta burst stimulation (TBS) will be randomized in a 1:1 ratio to either a tapered or clustered maintenance TBS protocol. Both groups receive the same total number of maintenance sessions over the same treatment period but differ in the temporal distribution of stimulation sessions
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Diagnosis of a depressive syndrome * Completion of an acute treatment course consisting of 20 sessions of theta burst stimulation (TBS) over 4 weeks * Response or remission following acute treatment. Response is defined as a ≥50% reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score * Remission is defined as a MADRS total score ≤10. * Clinical eligibility for maintenance TBS * Provision of written informed consent
Exclusion criteria
* Non-response to acute TBS treatment * Contraindications to transcranial magnetic stimulation (TMS) or theta burst stimulation (TBS) * Active substance use disorder (substance use within the past 3 months) * Acute psychiatric or medical conditions that preclude study participation Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to depressive relapse or clinically relevant symptom worsening | From randomization through Week 24 | Time from randomization to the first occurrence of depressive relapse or clinically relevant symptom worsening during the 24-week follow-up period. Clinically relevant symptom worsening is defined as a transition to a higher depression severity category together with an increase of at least 5 points in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Relapse is defined as recurrence of at least moderate depressive symptoms (MADRS ≥20) together with loss of the previously achieved treatment response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montgomery-Åsberg Depression Rating Scale Total Score | Baseline and Weeks 4, 8, 12, 16, 20, and 24 | Change in depressive symptom severity as assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). The MADRS total score ranges from 0 to 60, with higher scores indicating greater severity of depressive symptoms. |
| Change in Beck Depression Inventory II Total Score | Baseline and Weeks 4, 8, 12, 16, 20, and 24 | Change in patient-reported depressive symptom severity as assessed using the Beck Depression Inventory II Scale. Higher total scores indicate greater severity of depressive symptoms. |
| Change in Global Assessment of Functioning Score (GAF) | Baseline and Weeks 4, 8, 12, 16, 20, and 24 | Change in psychosocial functioning as assessed using the Global Assessment of Functioning scale. Scores range from 0 to 100, with lower scores indicating greater impairment in psychosocial functioning. |
| Change in Clinical Global Impression Score (CGI) | Baseline and Weeks 4, 8, 12, 16, 20, and 24 | Change in global clinical status as assessed using the Clinical Global Impression scale. |
| Change in Resting-State Functional Connectivity | During Maintenance rtMS Week 0-24 | Change in resting-state functional connectivity derived from functional magnetic resonance imaging. |
| Change in Cerebral Perfusion Measured by Arterial Spin Labeling | During maintenance treatment week 0-24 | Change in cerebral perfusion parameters derived from arterial spin labeling magnetic resonance imaging. |
| Change in Diffusion MRI Measures of Structural Connectivity and Microstructure | during maintenance treatment week 0 to 24 | Change in structural connectivity and tissue microstructure measures derived from diffusion imaging, including neurite orientation dispersion and density imaging. |
| Change in Quantitative MRI Parameters | During maintenance treatment week 0-24 | Change in quantitative magnetic resonance imaging parameters, including T1 mapping, T2 mapping, and magnetization transfer mapping. |
Countries
Germany
Contacts
CONTACTUlrike Vogelmann, Senior physician
Outcome results
None listed